IAI Accepts, published online ahead of print on 19 October 2009

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Infect. Immun. doi:10.1128/IAI.00904-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The effect of MarA-like proteins on antibiotic resistance and virulence in Yersinia pestis.

Ida M. Lister, Joan Mecsas, and Stuart B. Levy^*

Center for Adaptation Genetics and Drug Resistance and Departments of Molecular Biology and Microbiology and of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111

MarA, an AraC/XylS transcriptional regulator in Escherichia coli, affects drug susceptibility and virulence. Two MarA-like proteins have been found in Yersinia pestis: MarA47 and MarA48. Deletion or overexpression of these proteins in the attenuated KIM 1001 pgm- strain led to a change in multidrug susceptibility (including to clinically relevant drugs). Additionally, lung colonization by the marA47 or marA48 deletion mutant was decreased about 10 fold in a pneumonic plague mouse model. Complementation of the deletions by replacing the deleted genes on the chromosome restored wild type characteristics. These findings show that two MarA homologs in Y. pestis affect antibiotic susceptibility and virulence.